Several problems related to viral tumorigenesis will be investigated. 1) Simian Virus 40 (SV40) structural genes and signals for replication and transcription will be located in the genome by use of deletion mutants and point mutants and by nucleotide sequence determination. 2) Integration of SV40 DNA into cellular DNA will be studied by isolation of viral DNA-cell DNA fragments, and integration sites will be defined by mapping and nucleotide sequencing. 3) The fine structure of adeno-associated virus DNA will be determined by nucleotide sequence analysis and related to replication, transcription and possible integration of the DNA. 4) An in vitro system for DNA recombination will be explored using Hemophilus influenzae extracts. 5) Protein-nucleic acid recognition will be studied using restriction and modification enzymes and synthetic polydeoxynucleotides. 6) The role of DNA enzymes involved in DNA repair and possibly recombination in E. coli will be further characterized, particularly exonuclease III/endonuclease II. 7) Transducing animal viruses will be constructed and cloned using defined segments of SV40 DNA joined to other DNA molecules. BIBLIOGRAPHIC REFERENCES: Lee, T. N. H., Brockman, W. W., and Nathans, D. (1975). Evolutionary variants of Simian Virus 40: Cloned substituted variants containing multiple initiation sites for DNA replication. Virology 66, 53-69. Lai, C.-J., and Nathans, D. (1975). A map of temperature-sensitive mutants of Simian Virus 40. Virology 66, 70-81.